In the field of mass spectrometry, a technique called the MS/MS analysis (or tandem analysis) is widely known. Generally, an MS/MS analysis is conducted as follows: Initially, an ion having a specific mass-to-charge ratio (m/z) is selected from various kinds of ions generated from an object to be analyzed. Then, the selected ion, which is called the precursor ion, is dissociated into product ions by an appropriate process, e.g. collision-induced dissociation (CID). The product ions thus created are subjected to mass analysis to obtain information about the molecular structure of the objective ion. In the case of ion trap mass spectrometers, the CID process can take place within an ion trap having the function of confining ions.
The principle of ion selection by the ion trap mass spectrometer is now explained. Suppose a typical three-dimensional quadrupole ion trap is placed in a cylindrical coordinate system (r, Z), as shown in FIG. 2. This ion trap 1 includes a circular ring electrode 2, whose inner surface is in the form of a hyperboloid of revolution of one sheet, and a pair of end-cap electrodes 3 and 4 facing each other across the ring electrode 2, whose inner surfaces are in the form of a hyperboloid of revolution of two sheets. The space surrounded by these electrodes 2, 3 and 4 is the ion-trapping space 5. Now, suppose that an ion-capturing radio-frequency (RF) voltage U−V cos Ωt (which may be simply called the “ion-capturing voltage” hereinafter) is applied to the ring electrode 2, as shown.
The motions of various kinds of ions within a quadrupole electric field created within the ion-trapping space 5 by applying the ion-capturing voltage can be described by the following independent equations of motions (1) and (2) for the Z and r directions, respectively:d2r/dt2+(z/mr02)(U−V cos Ωt)r=0  (1)d2Z/dt2+(2z/mr02)(U−V cos Ωt)Z=0  (2),where m is the mass of the ion, z is the charge of the ion, and r0 is the inscribed circle diameter of the ring electrode 2. Now, let az, ar, qz, and qr be defined by the following equations (3) and (4):az=−2ar=−8U/[(m/z)r02Ω2]  (3)qz=−2qr=4V/[(m/z)r02Ω2]  (4).Then, the equations of motions (1) and (2) can be rewritten in the form of the following Mathieu equations (5) and (6):d2r/dζ2+(ar−2qr cos2ζ)r=0  (5)d2Z/dζ2+(az−2qz cos2ζ)Z=0  (6),where ζ=(Ωt)/2.
The natures of the solutions of these Mathieu equations can be expressed using az and qz. FIG. 3 is a graph illustrating stability conditions of the solutions of the Mathieu equations, with az as the coordinate and qz as the abscissa. The area S surrounded by the solid line on the az-qz plane in FIG. 3 gives the stability solutions of the previous equations. That is, for an ion with a mass-to-charge ratio m/z, the previous equations determine the parameters az and qz, and if the value pair (az, qz) lies within a specific area, the ion will be captured within the ion-trapping space 5, continuing its oscillation at a specific frequency. Specifically, the stability area S defined by the solid line is the area where ions can stay within the ion-trapping space 5 in a stable manner, and the surrounding area is the instability area where ions will be dispersed.
If the direct-current component U of the ion-capturing voltage is zero, then az=0 on the az-qz plane in FIG. 3, which means that the q axis indicated by Q in FIG. 3 is the only condition to be considered. In the case of a conventional analogue ion trap (which is abbreviated as the “AIT” hereinafter) using a sinusoidal RF voltage as the ion-capturing voltage, the boundary of the stability area S is at qz=0.908 (point P on the q axis). Therefore, any ion whose mass-to-charge ratio yields a qz value equal to or greater than 0.908 does not meet the trapping condition and cannot be captured. In equation (4), the mass-to-charge ratio m/z appears in the denominator, which means that any ion whose m/z is equal to or less than a specific value (called the “low mass cutoff” or LMC) will not be trapped. Theoretically, the value of LMC can be regulated by changing the amplitude V or frequency Ω of the RF component of the ion-capturing voltage. However, it is practically difficult for AITs to change the frequency Ω. Therefore, the amplitude V is usually changed to regulate the LMC value.
For a digital ion trap (DIT), in which a square-wave RF voltage is applied to the ring electrode 2 as the ion-capturing voltage, it is known that the theories applicable to the AIT also hold true, except that qz has a smaller value (0.7125) at the boundary of the stability area S (refer to Non-Patent Document 1 or other documents). In the DIT, the LMC value can be regulated at will by changing the frequency Ω of the ion-capturing voltage.
Under the previously described conditions, a CID reaction for dissociating the objective ion of a specific mass-to-charge ratio, which is trapped within the ion-trapping space 5, can be induced by applying to the end-cap electrodes 3 and 4 an RF voltage of frequency Ωex that resonates with the secular frequency Ωs of the objective ion. The frequency Ωex is signified by the following equation (7):Ωex=Ωs=(1/2)βzΩ  (7),where the parameter βz represents the Z-directional oscillation of the ion, as shown in FIG. 3. Ions are stable within the range 0<βz<1. The electric field created in the trap space 5 by the RF voltage causes resonant excitation of the objective ion, which collides with a rare gas. Thus, the objective ion is dissociated by CID into various product ions (fragment ions) having smaller mass-to-charge ratios than that of the objective ion.
When trapped in the ion-trapping space 5 as described previously, the ion senses a potential well created by the ion-capturing voltage. The depth Dz of this well depends on the value of qz (which is called the “q-value” hereinafter). It is generally known that a larger q-value produces a deeper potential well, in which ions are accelerated to higher speeds by resonant excitation and gain more kinetic energy, so that the dissociation efficiency improves (refer to Non-Patent Document 2 or other documents). In other words, the dissociation efficiency can be improved by trapping the objective ion with the highest possible q-value. However, increasing the q-value also increases the LMC value and thereby makes it more difficult to trap product ions resulting from dissociation whose mass-to-charge ratios are smaller than the LMC value.
To determine the amino acid sequence of a protein by an MS/MS (or MSn) analysis, it is also important to obtain information about product ions having small mass-to-charge ratios. In such cases, the analysis must be also performed with a smaller LMC value so as to cover small mass-to-charge ratios. To analyze such low-mass product ions, it is necessary to trap the objective ion with the lowest possible q-value, even through this operation deteriorates to some extent the dissociation efficiency. Thus, in setting the q-value, it is impossible to simultaneously satisfy the two requirements of improving the dissociation efficiency and decreasing the lower limit of the mass range (mass-to-charge ratio range) to be analyzed. Such a trade-off between the dissociation efficiency and the lower limit of the mass range has been conventionally taken into account in selecting a q-value for a dissociating operation.
Non-Patent Document 1: L. Ding et al., “A digital ion trap mass spectrometer coupled with atmospheric pressure ion sources”, J Mass Spectrom., 39 (2004), pp. 471-484
Non-Patent Document 2: V. M. Doroshenko et al., “Pulsed gas introduction for increasing peptide CID efficiency in a MALDI/quadrupole ion trap mass spectrometer”, Anal. Chem., 68 (1996), pp. 463-472